A series of experiments is proposed whose results will form the framework for developing appropriate therapy to optimize cardiac function in stressed newborns. An isolated, perfused, working newborn piglet heart model has been established for studies of cardiac metabolism and function. Metabolic studies will include investigations of substrate utilization, pathways of metabolism, and the rate-limiting steps within those pathways. Initial studies will be performed using single substrates and insulin in the perfusate. Utilization of endogenous and exogenous substrates will be determined. The importance of insulin in glucose utilization and glycogen storage will then be investigated. Thereafter, preferential substrate utilization will be investigated when mixed substrates are provided in the buffer. Initial studies will be performed in well-oxygenated hearts at physiologic pH. Initially, right ventricular pressure will be adjusted to be equal to that of the left ventricle. Subsequently, alterations will be made in both the perfusate and in outflow resistance in order to simulate the stressful states of acidosis, hypoxia, and evaluated right ventricular afterload. These conditions are similar to those observed in newborns with pulmonary parenchymal disease. Studies similar to those outlined above for the non-stressed heart will be performed under these altered physiologic states. The perfusion apparatus will then be modified in order to perform comparable investigations of fetal pig hearts obtained at 0.9 gestation.